ArticleJournal of orthopaedic research : official publication of the Orthopaedic Research Society2023
A2M inhibits inflammatory mediators of chondrocytes by blocking IL-1β/NF-κB pathway.
Article in Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- A first-in-human, prospective pilot trial of umbilical cord-derived mesenchymal stem cell eye drops therapy for patients with refractory non-Sjögren's and Sjögren's syndrome dry eye disease.Stem cell research & therapy · 2025Trial
- Alpha-2-Macroglobulin-Enriched Plasma Modulates Inflammatory and Proteolytic Pathways in Experimental Equine Musculoskeletal Models.Animals : an open access journal from MDPI · 2026Article
- Ultrasound-Guided Hydrodissection for Carpal Tunnel Syndrome with Bifid Median Nerve and Persistent Median Artery: An Imaging-Based Case Report with Alpha-2 Macroglobulin.Diagnostics (Basel, Switzerland) · 2026Article
- PCOS combined with obesity aggravates the metabolic and immune abnormality in females.BMC women's health · 2026Article
- Review
- Alpha2EQ downregulates proinflammatory cytokine and chemokine gene expression in cultured synovial fibroblasts.American journal of veterinary research · 2026Article
- Evidence for alpha-2-macroglobulin as an orthobiologic osteoarthritis therapy: a narrative review.American journal of veterinary research · 2026Review
- Synovial fluid alpha-2-macroglobulin, gelsolin and lubricin distinguish between osteoarthritic and healthy equine joints.Equine veterinary journal · 2026Article
- Extraction of platelet-rich plasma retaining physiological-concentration erythrocytes and enriched leukocytes enhances its functional capabilities.Journal of orthopaedic surgery and research · 2025Article
- Regenerative Medicine: The Next Generation of Autologous Blood Formulations.HSS journal : the musculoskeletal journal of Hospital for Special Surgery · 2025Review
- Molecular Dynamics Modeling of Potential Osteoarthritic Biomarkers.Life (Basel, Switzerland) · 2025Article
- Human dental pulp stem cells attenuate airway inflammation in mice with PMStem cell research & therapy · 2025Article
- Identification of pivotal genes and regulatory networks associated with SAH based on multi-omics analysis and machine learning.Scientific reports · 2025Article
- Proteomic profiling of human plasma and intervertebral disc tissue reveals matrisomal, but not plasma, biomarkers of disc degeneration.Arthritis research & therapy · 2025Article
- Increasing the concentration of plasma molecules improves the biological activity of platelet-rich plasma for tissue regeneration.Scientific reports · 2025Article
- Sex-specific gene expression and weighted co-expression network analysis suggest distinct sex-specific molecular signatures in acutely suicidal MDD-patients without somatic comorbidities.Frontiers in genetics · 2025Article
- Alpha-2-Macroglobulin Attenuates Posttraumatic Osteoarthritis Cartilage Damage by Inhibiting Inflammatory Pathways With Modified Intra-articular Drilling in a Yucatan Minipig Model.The American journal of sports medicine · 2024Article
- Proteomic Profiling of Tears in Blau Syndrome Patients in Identification of Potential Disease Biomarkers.International journal of molecular sciences · 2024Article
- The Effects of an Osteoarthritic Joint Environment on ACL Damage and Degeneration: A Yucatan Miniature Pig Model.Biomolecules · 2023Article
- α-parvin controls chondrocyte column formation and regulates long bone development.Bone research · 2023Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
A hallmark of osteoarthritis (OA) is cartilage degeneration, which has been previously correlated with dramatic increases in inflammatory enzymes. Specifically, interleukin-1β (IL-1β) and subsequent upregulation of nuclear factor kappa B (NF-κB) is implicated as an important player in the development of posttraumatic osteoarthritis (PTOA). Alpha 2-macroglobulin (A2M) can inhibit this inflammatory pathway, making it a promising therapy for PTOA. Herein, we demonstrate that A2M binds and neutralizes IL-1β, blocking downstream NF-κB-induced catabolism seen in in vitro. Human chondrocytes (cell line C28) were incubated with A2M protein and then treated with IL-1β. A2M was labeled with VivoTag™ 680 to localize the protein postincubation. The degree of binding between A2M and IL-1β was evaluated through immunoprecipitation (IP). Catabolic proteins, including IL-1β and NF-kB, were detected by Western blot. Pro-inflammatory and chondrocyte-related gene expression was examined by qRT-PCR. VivoTag™ 680-labeled A2M was observed in the cytoplasm of C28 human chondrocytes by fluorescence microscopy. IP experiments demonstrated that A2M could bind IL-1β. Additionally, western blot analysis revealed that A2M neutralized IL-1β and NF-κB in a dose-dependent manner. Moreover, A2M decreased levels of MMPs and TNF-α and increased the expression of cartilage protective genes Col2, Type2, Smad4, and aggrecan. Mostly importantly, A2M was shown to directly neutralize IL-1β to downregulate the pro-inflammatory responses mediated by the NF-kB pathway. These results demonstrate a mechanism by which A2M reduces inflammatory catabolic activity and protects cartilage after joint injury. Further in vivo studies are needed to fully understand the potential of A2M as a novel PTOA therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.